In an Early Edition publication of The Proceedings of the National Academy of Sciences (PNAS) this week, the researchers demonstrate the "alpha-synuclein dance" the switching back and forth of the protein between a bent helix and an extended helix as the surface that it is binding to changes.
Such shape shifting has rarely been so directly observed in proteins like alpha-synuclein, which are known to be unfolded in isolation, says the study's senior investigator Ashok Deniz, an associate professor at The Scripps Research Institute.
"We are intrigued to see such complex behavior," he says. "It is interesting that with just a single binding partner, the protein can undergo so many dramatic shape transitions, and that the whole process is reversible."
In the past, scientists believed that proteins, as directed by their genes, fold themselves into defined three-dimensional structures that dictate their function. But more recently, a class of proteins known as "intrinsically disordered proteins" have been identified, which are functional, despite the fact that they are often unfolded.
Alpha-synuclein is such a protein. Mutations in the gene that produces alpha-synuclein have been linked to early-onset Parkinson's disease, and in sporadic, common Parkinson's disease, the protein can accumulate into so-called Lewy bodies inside nerve cells. The protein is also found in the amyloid plaques in Alzheimer's disease, and in other forms of neurological disease.
To learn more about alpha-synuclein, the Scripps Research team decided to study the shape of single proteins. To do this, they used a technique they helped develop, which is known as single-molecule fluorescence resonance energy transfer (FRET), to look at how the protein folds when it binds to different molecules. This technique, which Deniz calls a "molecular ruler," measures light emitted from fluorescent dyes that are attached to amino acids in the pr
|Contact: Keith McKeown|
Scripps Research Institute